CN113840603A - 嘧啶并五元氮杂环类衍生物、其制备方法及其在医药上的应用 - Google Patents
嘧啶并五元氮杂环类衍生物、其制备方法及其在医药上的应用 Download PDFInfo
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- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 238000011369 optimal treatment Methods 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 125000004585 polycyclic heterocycle group Chemical group 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012354 sodium borodeuteride Substances 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000012089 stop solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000025366 tissue development Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
嘧啶并五元氮杂环类衍生物、其制备方法及其在医药上的应用。具体为通式(II)所示的嘧啶并五元氮杂环类衍生物、其制备方法、含有该衍生物的组合物，其作为SHP2抑制剂及其用于制备预防和/或治疗肿瘤或者癌症的药物中的用途。
Description
PCT国内申请，说明书已公开。
Claims (16)
- PCT国内申请，权利要求书已公开。
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910577816 | 2019-06-28 | ||
| CN2019105778163 | 2019-06-28 | ||
| CN202010296869 | 2020-04-15 | ||
| CN2020102968690 | 2020-04-15 | ||
| CN202010466633 | 2020-05-28 | ||
| CN2020104666337 | 2020-05-28 | ||
| PCT/CN2020/098474 WO2020259679A1 (zh) | 2019-06-28 | 2020-06-28 | 嘧啶并五元氮杂环类衍生物、其制备方法及其在医药上的应用 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113840603A true CN113840603A (zh) | 2021-12-24 |
Family
ID=74059660
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202080036459.0A Pending CN113840603A (zh) | 2019-06-28 | 2020-06-28 | 嘧啶并五元氮杂环类衍生物、其制备方法及其在医药上的应用 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US20220380385A1 (zh) |
| EP (1) | EP3991731A4 (zh) |
| JP (1) | JP2022538548A (zh) |
| KR (1) | KR20220054285A (zh) |
| CN (1) | CN113840603A (zh) |
| AU (1) | AU2020306124A1 (zh) |
| BR (1) | BR112021024674A2 (zh) |
| CA (1) | CA3144284A1 (zh) |
| TW (1) | TW202115076A (zh) |
| WO (1) | WO2020259679A1 (zh) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP4169920A1 (en) * | 2020-06-18 | 2023-04-26 | Etern Biopharma (Shanghai) Co., Ltd. | Crystalline form of shp2 inhibitor, and composition thereof, preparation method therefor, and use thereof |
| IL299131A (en) | 2020-06-18 | 2023-02-01 | Revolution Medicines Inc | Methods for delaying, preventing and treating acquired resistance to RAS inhibitors |
| MX2023002248A (es) | 2020-09-03 | 2023-05-16 | Revolution Medicines Inc | Uso de inhibidores de sos1 para tratar neoplasias malignas con mutaciones de shp2. |
| PE20231207A1 (es) | 2020-09-15 | 2023-08-17 | Revolution Medicines Inc | Derivados indolicos como inhibidores de ras en el tratamiento del cancer |
| TW202241902A (zh) * | 2020-12-25 | 2022-11-01 | 大陸商江蘇恒瑞醫藥股份有限公司 | 一種嘧啶并五元氮雜環類衍生物的晶型及其製備方法 |
| CA3206933A1 (en) * | 2021-02-05 | 2022-08-11 | Guangxiu Dai | Tricyclic compounds and uses thereof |
| AR125782A1 (es) | 2021-05-05 | 2023-08-16 | Revolution Medicines Inc | Inhibidores de ras |
| AU2022268962A1 (en) | 2021-05-05 | 2023-12-14 | Revolution Medicines, Inc. | Ras inhibitors for the treatment of cancer |
| EP4334324A1 (en) | 2021-05-05 | 2024-03-13 | Revolution Medicines, Inc. | Covalent ras inhibitors and uses thereof |
| WO2022241975A1 (en) * | 2021-05-20 | 2022-11-24 | Etern Biopharma (Shanghai) Co., Ltd. | Methods for treating cancers associated with egfr mutation |
| WO2022259157A1 (en) | 2021-06-09 | 2022-12-15 | Novartis Ag | A triple pharmaceutical combination comprising dabrafenib, trametinib and a shp2 inhibitor |
| TW202317100A (zh) | 2021-06-23 | 2023-05-01 | 瑞士商諾華公司 | 包含ｋｒａｓ ｇ１２ｃ抑制劑的藥物組合及其用於治療癌症之用途 |
| WO2023025290A1 (zh) * | 2021-08-27 | 2023-03-02 | 江苏恒瑞医药股份有限公司 | Shp2抑制剂治疗含有ras通路基因突变的肿瘤的用途 |
| WO2023031781A1 (en) | 2021-09-01 | 2023-03-09 | Novartis Ag | Pharmaceutical combinations comprising a tead inhibitor and uses thereof for the treatment of cancers |
| AR127308A1 (es) | 2021-10-08 | 2024-01-10 | Revolution Medicines Inc | Inhibidores ras |
| WO2023172940A1 (en) | 2022-03-08 | 2023-09-14 | Revolution Medicines, Inc. | Methods for treating immune refractory lung cancer |
| WO2023230968A1 (zh) * | 2022-06-01 | 2023-12-07 | 上海凌达生物医药有限公司 | Shp2抑制剂、其晶型及其制备方法与用途 |
| WO2023240263A1 (en) | 2022-06-10 | 2023-12-14 | Revolution Medicines, Inc. | Macrocyclic ras inhibitors |
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| CN105142634A (zh) * | 2013-04-26 | 2015-12-09 | 美国印第安纳大学研究和技术公司 | 包含Src同源-2结构域的致癌性蛋白酪氨酸磷酸酶-2(SHP2)的基于羟基吲哚羧酸的抑制剂 |
| CN107660205A (zh) * | 2015-04-03 | 2018-02-02 | 因赛特公司 | 作为lsd1抑制剂的杂环化合物 |
| WO2018081091A1 (en) * | 2016-10-24 | 2018-05-03 | Relay Therapeutics, Inc. | Pyrazolo[3,4-b]pyrazine derivatives as shp2 phosphatase inhibitors |
| WO2018136265A1 (en) * | 2017-01-23 | 2018-07-26 | Revolution Medicines, Inc. | Bicyclic compounds as allosteric shp2 inhibitors |
| WO2018172984A1 (en) * | 2017-03-23 | 2018-09-27 | Jacobio Pharmaceuticals Co., Ltd. | Novel heterocyclic derivatives useful as shp2 inhibitors |
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| EP3016652A4 (en) | 2013-07-03 | 2017-03-08 | Indiana University Research and Technology Corporation | Shp2 inhibitors and methods of treating autoimmune and/or glomerulonephritis-associated diseases using shp2 inhibitors |
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| WO2018130928A1 (en) | 2017-01-10 | 2018-07-19 | Novartis Ag | Pharmaceutical combination comprising an alk inhibitor and a shp2 inhibitor |
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-
2020
- 2020-06-28 EP EP20832137.2A patent/EP3991731A4/en not_active Withdrawn
- 2020-06-28 KR KR1020227001970A patent/KR20220054285A/ko unknown
- 2020-06-28 JP JP2021575968A patent/JP2022538548A/ja active Pending
- 2020-06-28 BR BR112021024674A patent/BR112021024674A2/pt not_active Application Discontinuation
- 2020-06-28 AU AU2020306124A patent/AU2020306124A1/en not_active Abandoned
- 2020-06-28 WO PCT/CN2020/098474 patent/WO2020259679A1/zh active Application Filing
- 2020-06-28 CA CA3144284A patent/CA3144284A1/en active Pending
- 2020-06-28 CN CN202080036459.0A patent/CN113840603A/zh active Pending
- 2020-06-28 US US17/619,759 patent/US20220380385A1/en active Pending
- 2020-06-29 TW TW109121878A patent/TW202115076A/zh unknown
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| CN107660205A (zh) * | 2015-04-03 | 2018-02-02 | 因赛特公司 | 作为lsd1抑制剂的杂环化合物 |
| CN109311848A (zh) * | 2016-06-07 | 2019-02-05 | 北京加科思新药研发有限公司 | 可用作shp2抑制剂的新型杂环衍生物 |
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Also Published As
| Publication number | Publication date |
|---|---|
| WO2020259679A1 (zh) | 2020-12-30 |
| TW202115076A (zh) | 2021-04-16 |
| EP3991731A4 (en) | 2022-07-20 |
| BR112021024674A2 (pt) | 2022-05-31 |
| US20220380385A1 (en) | 2022-12-01 |
| CA3144284A1 (en) | 2020-12-30 |
| AU2020306124A1 (en) | 2022-02-03 |
| KR20220054285A (ko) | 2022-05-02 |
| JP2022538548A (ja) | 2022-09-05 |
| EP3991731A1 (en) | 2022-05-04 |
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